DegronMD - P10909(CLU)

FUNCTION: [Isoform 1]: Functions as extracellular chaperone that prevents aggregation of non native proteins (PubMed:11123922, PubMed:19535339). Prevents stress-induced aggregation of blood plasma proteins (PubMed:11123922, PubMed:12176985, PubMed:17260971, PubMed:19996109). Inhibits formation of amyloid fibrils by APP, APOC2, B2M, CALCA, CSN3, SNCA and aggregation-prone LYZ variants (in vitro) (PubMed:12047389, PubMed:17412999, PubMed:17407782). Does not require ATP (PubMed:11123922). Maintains partially unfolded proteins in a state appropriate for subsequent refolding by other chaperones, such as HSPA8/HSC70 (PubMed:11123922). Does not refold proteins by itself (PubMed:11123922). Binding to cell surface receptors triggers internalization of the chaperone-client complex and subsequent lysosomal or proteasomal degradation (PubMed:21505792). Protects cells against apoptosis and against cytolysis by complement (PubMed:2780565). Intracellular forms interact with ubiquitin and SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complexes and promote the ubiquitination and subsequent proteasomal degradation of target proteins (PubMed:20068069). Promotes proteasomal degradation of COMMD1 and IKBKB (PubMed:20068069). Modulates NF-kappa-B transcriptional activity (PubMed:12882985). A mitochondrial form suppresses BAX-dependent release of cytochrome c into the cytoplasm and inhibit apoptosis (PubMed:16113678, PubMed:17689225). Plays a role in the regulation of cell proliferation (PubMed:19137541). An intracellular form suppresses stress-induced apoptosis by stabilizing mitochondrial membrane integrity through interaction with HSPA5 (PubMed:22689054). Secreted form does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity (PubMed:24073260). Secreted form act as an important modulator during neuronal differentiation through interaction with STMN3 (By similarity). Plays a role in the clearance of immune complexes that arise during cell injury (By similarity). {ECO:0000250|UniProtKB:P05371, ECO:0000250|UniProtKB:Q06890, ECO:0000269|PubMed:11123922, ECO:0000269|PubMed:12047389, ECO:0000269|PubMed:12176985, ECO:0000269|PubMed:12882985, ECO:0000269|PubMed:16113678, ECO:0000269|PubMed:17260971, ECO:0000269|PubMed:17407782, ECO:0000269|PubMed:17412999, ECO:0000269|PubMed:17689225, ECO:0000269|PubMed:19137541, ECO:0000269|PubMed:19535339, ECO:0000269|PubMed:19996109, ECO:0000269|PubMed:20068069, ECO:0000269|PubMed:21505792, ECO:0000269|PubMed:22689054, ECO:0000269|PubMed:24073260, ECO:0000269|PubMed:2780565}.; FUNCTION: [Isoform 6]: Does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity. {ECO:0000269|PubMed:24073260}.; FUNCTION: [Isoform 4]: Does not affect caspase or BAX-mediated intrinsic apoptosis and TNF-induced NF-kappa-B-activity (PubMed:24073260). Promotes cell death through interaction with BCL2L1 that releases and activates BAX (PubMed:21567405). {ECO:0000269|PubMed:21567405, ECO:0000269|PubMed:24073260}. View more >>

GO - Biological processes (BP): cell morphogenesis [GO:0000902]; central nervous system myelin maintenance [GO:0032286]; chaperone-mediated protein complex assembly [GO:0051131]; chaperone-mediated protein folding [GO:0061077]; complement activation [GO:0006956]; complement activation, classical pathway [GO:0006958]; immune complex clearance [GO:0002434]; innate immune response [GO:0045087]; intrinsic apoptotic signaling pathway [GO:0097193]; lipid metabolic process [GO:0006629]; microglial cell activation [GO:0001774]; microglial cell proliferation [GO:0061518]; negative regulation of amyloid-beta formation [GO:1902430]; negative regulation of amyloid fibril formation [GO:1905907]; negative regulation of cell death [GO:0060548]; negative regulation of cellular response to thapsigargin [GO:1905892]; negative regulation of cellular response to tunicamycin [GO:1905895]; negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage [GO:1902230]; negative regulation of protein-containing complex assembly [GO:0031333]; negative regulation of release of cytochrome c from mitochondria [GO:0090201]; negative regulation of response to endoplasmic reticulum stress [GO:1903573]; positive regulation of amyloid-beta formation [GO:1902004]; positive regulation of amyloid fibril formation [GO:1905908]; positive regulation of apoptotic process [GO:0043065]; positive regulation of gene expression [GO:0010628]; positive regulation of intrinsic apoptotic signaling pathway [GO:2001244]; positive regulation of neurofibrillary tangle assembly [GO:1902998]; positive regulation of neuron death [GO:1901216]; positive regulation of NF-kappaB transcription factor activity [GO:0051092]; positive regulation of nitric oxide biosynthetic process [GO:0045429]; positive regulation of proteasomal ubiquitin-dependent protein catabolic process [GO:0032436]; positive regulation of protein-containing complex assembly [GO:0031334]; positive regulation of receptor-mediated endocytosis [GO:0048260]; positive regulation of tau-protein kinase activity [GO:1902949]; positive regulation of tumor necrosis factor production [GO:0032760]; positive regulation of ubiquitin-dependent protein catabolic process [GO:2000060]; protein import [GO:0017038]; protein stabilization [GO:0050821]; protein targeting to lysosome involved in chaperone-mediated autophagy [GO:0061740]; regulation of amyloid-beta clearance [GO:1900221]; regulation of apoptotic process [GO:0042981]; regulation of cell population proliferation [GO:0042127]; regulation of neuronal signal transduction [GO:1902847]; regulation of neuron death [GO:1901214]; release of cytochrome c from mitochondria [GO:0001836]; response to misfolded protein [GO:0051788]; response to virus [GO:0009615]; reverse cholesterol transport [GO:0043691] View more >>

GO - Molecular function (MF): View more >>

GO - Cellular component (CC): View more >>

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Open in full screen with detailed sequence annotations

Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.S400F	TCGA-3C-AALI	BRCA	TCGA	SHTSDSDVPSGV	DEG_COP1_1	391:402	Mutation altering degron motif	0.7982
p.R385W	TCGA-B5-A3FC	UCEC	TCGA	SHTSDSDVPSGV	DEG_COP1_1	391:402	Mutation rewiring degron network	0.1667
p.V389A	TCGA-CD-A4MG	STAD	TCGA	SHTSDSDVPSGV	DEG_COP1_1	391:402	Mutation rewiring degron network	0.2778
p.V398I	TCGA-KQ-A41R	BLCA	TCGA	SHTSDSDVPSGV	DEG_COP1_1	391:402	Mutation altering degron motif	0.7076
p.V409I	DO223592	BLCA	ICGC	SHTSDSDVPSGV	DEG_COP1_1	391:402	Mutation rewiring degron network	0.1389
p.S411F	DO219589	BRCA	ICGC	SHTSDSDVPSGV	DEG_COP1_1	391:402	Mutation rewiring degron network	0.0833
p.E390K	DO7934	COAD	ICGC	SHTSDSDVPSGV	DEG_COP1_1	391:402	Mutation rewiring degron network	0.3056
p.E390K	DO229035	LICA	ICGC	SHTSDSDVPSGV	DEG_COP1_1	391:402	Mutation rewiring degron network	0.3056
p.D391H	DO20897	KIRP	ICGC	SHTSDSDVPSGV	DEG_COP1_1	391:402	Mutation altering degron motif	0.7688
p.V400A	DO48009	STAD	ICGC	SHTSDSDVPSGV	DEG_COP1_1	391:402	Mutation altering degron motif	0.6936
p.R396W	DO41871	UCEC	ICGC	SHTSDSDVPSGV	DEG_COP1_1	391:402	Mutation altering degron motif	0.8634
p.S396L	SIDM01116	Non-Small Cell Lung Carcinoma	GDSC	SHTSDSDVPSGV	DEG_COP1_1	391:402	Mutation altering degron motif	0.7667
p.S396L	SIDM00690	Head and Neck Carcinoma	GDSC	SHTSDSDVPSGV	DEG_COP1_1	391:402	Mutation altering degron motif	0.7667
p.S396L	SIDM01147	Gastric Carcinoma	GDSC	SHTSDSDVPSGV	DEG_COP1_1	391:402	Mutation altering degron motif	0.7667
p.S396L	SIDM01605	Non-Small Cell Lung Carcinoma	GDSC	SHTSDSDVPSGV	DEG_COP1_1	391:402	Mutation altering degron motif	0.7667
p.V402I	SIDM00293	Small Cell Lung Carcinoma	GDSC	SHTSDSDVPSGV	DEG_COP1_1	391:402	Mutation altering degron motif	0.5965
p.V402I	ACH-002052	Lung Cancer	CCLE	SHTSDSDVPSGV	DEG_COP1_1	391:402	Mutation altering degron motif	0.5965
p.V402I	LU-139	lung	COSMIC	SHTSDSDVPSGV	DEG_COP1_1	391:402	Mutation altering degron motif	0.5965
p.Y383N	ACH-000634	Brain Cancer	CCLE	SHTSDSDVPSGV	DEG_COP1_1	391:402	Mutation rewiring degron network	0.1111

DegronMD: protein-targeted degradation, mutation and drug response to degrons

CLU

UniProt ID: P10909

Entrez ID: 1191

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for CLU in